Photosensitized biological processes, as applied in
photodynamic therapy, are based on light-triggered generation of molecular
singlet oxygen by a membrane-residing sensitizer. Most of the sensitizers currently used are hydrophobic or amphiphilic
porphyrins and their analogs. The possible activity of the short-lived
singlet oxygen is limited to the time it is diffusing in the membrane, before it emerges into the aqueous environment. In this paper we demonstrate the enhancement of the
photosensitization process that is obtained by newly synthesized
protoporphyrin derivatives, which insert their
tetrapyrrole chromophore deeper into the
lipid bilayer of
liposomes. The insertion was measured by fluorescence quenching by
iodide and the
photosensitization efficiency was measured with
9,10-dimethylanthracene, a fluorescent chemical target for
singlet oxygen. We also show that when the bilayer undergoes a melting phase transition, or when it is fluidized by
benzyl alcohol, the sensitization efficiency decreases because of the enhanced diffusion of
singlet oxygen. The addition of
cholesterol or of dimyristoyl phosphatydilcholine to the bilayer moves the
porphyrin deeper into the bilayer; however, the ensuing effect on the sensitization efficiency is different in these two cases. These results could possibly define an additional criterion for the choice and design of hydrophobic, membrane-bound
photosensitizers.